The immune system is both a source of malignancies and a tool for cancer therapy. The Immunology/lmmunotherapy Program (IMM) supports basic and clinical research to increase the understanding and control of (1) the immune response to cancer and (2) the ways hematopoietic cell development and its dysregulation can be used to treat hematologic malignancies. IMM Program members approach this two-faceted goal through three scientific Themes: (1) Development and Optimization of Antigen-Directed Immunotherapeutics; (2) Positive and Negative Regulation of the Quality of Anti-Tumor Immunity. (3) Control of Hematopoiesis and Hematologic Malignancies. These Themes include outstanding basic science investigations, as well as highly collaborative translational initiatives to develop clinical trials based on this research. Program Co-Leader, Victor Engelhard, PhD, is internationally recognized for his work in tumor antigen identification and induction of tumor-specific CD8 T cell responses. Program Co-leader, Craig Slingluff, MD, has made major contributions to cancer immunotherapy through both laboratory research and investigator-initiated clinical trials. The Program consists of 27 Full Members and 3 Associate Members from six departments in the School of Medicine. Total extramural funding for the Program exceeds $17 million, including $4 million from the National Cancer Institute (NCI). Program Members have produced 293 cancer-relevant publications, of which 21% were inter-programmatic and 19% were intra-programmatic since the last renewal. The Program supports research in progress presentations and seminars to engender new directions and collaborations; Pilot funding to encourage development of promising collaborations and ideas; and an Immune Monitoring Laboratory to facilitate clinical research. Seventeen investigator-initiated clinical trials led by Program Members, including two ECOG trials and three additional multicenter trials, have enrolled patients across six cancer histologies and evaluated peptide vaccines, cytokines, and antibodies. These trials test hypotheses arising from laboratory science and also bring tissue to the laboratories to investigate cellular processes and molecular mechanisms to explain the clinical findings. This Program provides a firm foundation for continued advances in both understanding of the immune system and utilizing that knowledge to improve immunotherapy and treatment of hematologic malignancies.